Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

Brody, Arthur L.; Mukhin, Alexey G.; Shulenberger, Stephanie; Mamoun, Michael; Kozman, Maggie; Phuong, Jonathan; Neary, Meaghan K.; Luu, Trinh; Mandelkern, M.

doi:10.1038/npp.2013.53

Cited by 28 publications

(19 citation statements)

References 65 publications

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“…For example, chronic smoking desensitizes nicotinic acetylcholinergic receptors and increases their density in the brain including the DLPFC (56–59), reduce gray matter density in the DLPFC (60, 61), and alter task-related activity of the DLPFC during an attentional task (62). Overnight abstinence from smoking may further alter functional activity of the DLPFC and other brain regions in tobacco dependent smokers and leads to withdrawal symptoms (63–67).…”

Section: Discussionmentioning

confidence: 99%

Transcranial Direct Current Stimulation Reduces Negative Affect but Not Cigarette Craving in Overnight Abstinent Smokers

Xu¹,

Fregni²,

Brody³

et al. 2013

Front. Psychiatry

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Transcranial direct current stimulation (tDCS) can enhance cognitive control functions including attention and top-down regulation over negative affect and substance craving in both healthy and clinical populations, including early abstinent (∼1.5 h) smokers. The aim of this study was to assess whether tDCS modulates negative affect, cigarette craving, and attention of overnight abstinent tobacco dependent smokers. In this study, 24 smokers received a real and a sham session of tDCS after overnight abstinence from smoking on two different days. We applied anode to the left dorsolateral prefrontal cortex and cathode to the right supra-orbital area for 20 min with a current of 2.0 mA. We used self-report questionnaires Profile of Mood States (POMS) to assess negative affect and Urge to Smoke (UTS) Scale to assess craving for cigarette smoking, and a computerized visual target identification task to assess attention immediately before and after each tDCS. Smokers reported significantly greater reductions in POMS scores of total mood disturbance and scores of tension–anxiety, depression–dejection, and confusion–bewilderment subscales after real relative to sham tDCS. Furthermore, this reduction in negative affect positively correlated with the level of nicotine dependence as assessed by Fagerström scale. However, reductions in cigarette craving after real vs. sham tDCS did not differ, nor were there differences in reaction time or hit rate change on the visual task. Smokers did not report significant side effects of tDCS. This study demonstrates the safety of tDCS and its promising effect in ameliorating negative affect in overnight abstinent smokers. Its efficacy in treating tobacco dependence deserves further investigation.

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Section: Discussionmentioning

confidence: 99%

Transcranial Direct Current Stimulation Reduces Negative Affect but Not Cigarette Craving in Overnight Abstinent Smokers

Xu¹,

Fregni²,

Brody³

et al. 2013

Front. Psychiatry

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“…For demographic and smoking-related information, the Smokers' Profile Form was administered, as in past studies of smoking cessation treatment. [41][42][43] Smoking behavior was assessed with an exhaled carbon monoxide (CO) level (MicroSmokerlyzer, Bedfont Scientific Ltd, Kent, United Kingdom) and the Fagerström Test for Nicotine Dependence (FTND). 44,45 While some investigators have questioned the use of the standard FTND in smokers with schizophrenia, 46,47 there is considerable support in the literature for its use.…”

Section: Baseline and Treatment-related Assessmentsmentioning

confidence: 99%

“…13,42,62 Psychotherapy consisted of 12 rotating sessions focused on: education about smoking addiction, withdrawal, and relapse prevention; recognizing danger situations (triggers) that could lead to relapse; developing new coping skills, such as avoiding triggers, coping with negative affective states, reducing overall stress, and distracting attention from smoking using thought-stopping techniques; developing lifestyle changes; and social support. 63,64 Participants had exhaled CO levels monitored at each session, and were encouraged to taper off cigarettes.…”

Section: Study Treatmentsmentioning

confidence: 99%

Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial

Brody

Zorick

Hubert

et al. 2016

NICTOB

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Introduction: The majority of people with schizophrenia have a diagnosis of tobacco dependence during their lifetime. A major obstacle to reducing the burden of cigarette smoking in this population is that these smokers have lower quit rates when undergoing standard treatment compared to smokers with no mental illness. We sought to determine if combination extended treatment (COMB-EXT) and home visits (HV) would lead to improved outcomes in smokers with schizophrenia. Methods: Thirty-four cigarette smokers with schizophrenia completed either COMB-EXT with HV, COMB-EXT without HV, or treatment as usual (TAU) (random assignment). COMB-EXT consisted of group cognitive-behavioral therapy (CBT), bupropion, nicotine patch, and nicotine lozenge, which were initiated within 2 weeks and continued for 26 weekly visits. HV consisted of biweekly visits to the home with assessment of secondhand smoke (SHS) exposure and brief behavioral therapy with participants and others in the home environment. TAU consisted of group CBT plus serial single or combination medication trials as per standard care. Results: Smokers with schizophrenia who received COMB-EXT (with or without HV) had greater reductions in cigarettes per day than those treated with TAU (both ps < .01). In addition, 7-day point prevalence abstinence rates for the three groups were 45%, 20%, and 8%, respectively, which was significantly higher for COMB-EXT plus HV than TAU (χ 2 (1) = 4.8, p = .03). Groups did not differ significantly in the number of adverse events, and HV were easily scheduled. Conclusion: COMB-EXT improves outcomes for smokers with schizophrenia. HV appeared to provide additional benefit for smoking cessation in this treatment-resistant population. Implications: The clear benefit found here of rapidly initiated, combination, extended treatment over TAU suggests that aggressive and extended treatment should be considered in clinical practice for smokers with schizophrenia. Furthermore, HV to address SHS exposure showed initial promise for assisting smokers with schizophrenia in maintaining abstinence, indicating that this intervention may be worthy of future research.

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“…The first of these studies [146] focused on changes in nAChR density from pre- to post- treatment with either cognitive-behavioral therapy, bupropion, or placebo. In an exploratory analysis, pre-treatment markers for nAChR density had trend-level indications that lower nAChR density in three brain regions studied was associated with a greater likelihood of quitting.…”

Section: Brain Imaging Biomarkersmentioning

confidence: 99%

Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date

et al. 2015

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For the past thirty years, research examining predictors of successful smoking cessation treatment response has focused primarily on clinical variables, such as levels of tobacco dependence, craving, and self-efficacy. Recent research, however, has begun to determine biomarkers (such as genotype, nicotine and metabolite levels, and brain imaging findings) that may have utility in predicting smoking cessation. For genotype, genes associated with nicotinic acetylcholine receptors (nAChRs) and related proteins have been found to predict response to first line medications (e.g., nicotine replacement therapy [NRT], bupropion, or varenicline) or quitting over time without a controlled treatment trial. For nicotine and metabolite levels, function of the CYP 2A6 liver enzyme, which can be assessed with the nicotine metabolite ratio or via genotype, has been found to predict response, with slow nicotine metabolizers having less severe nicotine dependence and a greater likelihood of quitting with NRT than normal metabolizers. And for brain imaging, decreased activation of brain regions associated with emotion regulation and increased connectivity in emotion regulation networks, increased responsiveness to pleasant cues, and altered activation with the Stroop effect have been found in smokers who quit with the first-line medications listed above or counseling. In addition, our group recently demonstrated that lower pre-treatment brain nAChR density is associated with a greater chance of quitting smoking with NRT or placebo. Several of these studies found that specific biomarkers may provide additional information for predicting response beyond subjective symptom or rating scale measures, thereby giving an initial indication that biomarkers may, in the future, be useful for guiding smoking cessation treatment intensity, duration, and type.

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Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

Cited by 28 publications

References 65 publications

Transcranial Direct Current Stimulation Reduces Negative Affect but Not Cigarette Craving in Overnight Abstinent Smokers

Transcranial Direct Current Stimulation Reduces Negative Affect but Not Cigarette Craving in Overnight Abstinent Smokers

Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial

Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date

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